The candidate's long term goals are the development of novel diagnostic and therapeutic approaches to lymphoid malignancies based on the study of lymphocyte migration. The current proposal outlines experiments which will (1)complete the characterization of an adhesive site on the lymphocyte surface which contributes to cellular migration; (2)begin the characterization of the complementary adhesive site on the surface of the high endothelial venules (HEV), the specialized post-capillary venule through which the bulk of lymphocyte migration takes place; and (3)determine whether a causal relationship exists between the attachment of malignant lymphocytes to HEV and the hematogenous dissemination of lymphoid malignancies. Specifically, the hypothesis that lectins on the lymphocyte surface participate in the attachement to HEV will be verified using labelled polysaccharide, glycoprotein and antibody probes. The activity (number and affinity) of the membrane receptor will be correlated with binding acitivity (to HEV in vitro) and migratory activity (into lymphoid organ in vivo). Furthermore, immunochemical methods will be used to determine whether the phosphomannosyl receptor implicated in lymphocyte migration is similar to the hepatic phosphomannosyl receptor implicated in intracellular trafficing. The HEV project will attempt to purify and culture this specialized microvasculature as a first step in the study of the adhesive site on these cells. Finally, the mechanism underlying the hematogenous dissemination of lymphoid malignancies will be explored by correlating the binding activity towards HEV with the subsequent development of metastatic disease in lymphoid organs. A variety of murine radiation-leukemia virus transformed cell lines will be used initially. In addition, an attempt will be made to clone malignant cells on the basis of binding activity towards HEV and expression of the putative adhesive lectin.